Extrathymic origin of human gamma delta T cells during fetal development.

Extrathymic origin of human gamma delta T cells during fetal development.
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DOI:
10.4049/jimmunol.157.7.2873
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发表时间:
1996-10
影响因子:
4.4
通讯作者:
L. McVay;S. Carding
L. McVay;S. Carding
中科院分区:
医学2区
文献类型:
--
作者:
L. McVay;S. Carding

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We have identified the first TCRs to be generated in vivo during normal human fetal development. Before thymic formation, the liver is a site of generation for a subset of V gamma 9/V delta 2+ gamma delta T cells. Analysis of the expression of the male-specific gene, SRY, by V gamma 9/V delta 2+ gamma delta T cells isolated from the fetal liver of male donors has shown that these cells are generated de novo in the liver. Examination of TCR-V gamma and -V delta gene expression demonstrated that although multiple receptor rearrangements could be detected, V gamma 9-JP- and V delta 2-D delta 3-J delta 1/3-encoded receptors were preferentially expressed in each of five individual liver samples. Structural analysis of these receptor chains and those expressed by a panel of V gamma 9/V delta 2+ fetal T cell clones showed that the V gamma 9-JP receptors were invariant or canonical and that the delta-chains contained non-germ line-encoded structural motifs. gamma delta T cells expressing these structurally limited receptor chains were shown to be functional and capable of responding to mycobacterial Ags. Together with the observation that V gamma 9/V delta 2+ cells represented the majority of T cells present in the fetal liver between 7 and 11 wk of development, our findings demonstrate that this subset of gamma delta T cells is a major, and presumably important, component of the human fetal immune system.